Is it all the RAGE? Defining the role of the receptor for advanced glycation end products in Parkinson’s disease

Authors

Gasparotto J, Somensi N, Girardi CS, Bittencourt RR, de Oliveira LM, Hoefel LP, Scheibel IM, Peixoto DO, Moreira JCF, Outeiro TF, Gelain DP

Journal

Journal of Neurochemistry

Citation

J Neurochem. 2023 Jun 28.

Abstract

The receptor for advanced glycation end products (RAGE) is a transmembrane receptor that belongs to the immunoglobulin superfamily and is extensively associated with chronic inflammation in non-transmissible diseases. As chronic inflammation is consistently present in neurodegenerative diseases, it was largely assumed that RAGE could act as a critical modulator of neuroinflammation in Parkinson’s disease (PD), similar to what was reported for Alzheimer’s disease (AD), where RAGE is postulated to mediate proinflammatory signaling in microglia by binding to amyloid-β peptide.
However, accumulating evidence from studies of RAGE in PD models suggests a less obvious scenario. Here, we review physiological aspects of RAGE and address the current questions about the potential involvement of this receptor in the cellular events that may be critical for the development and progression of PD, exploring possible mechanisms beyond the classical view of the microglial activation/neuroinflammation/neurodegeneration axis that is widely assumed to be the general mechanism of RAGE action in the adult brain.

DOI

10.1111/jnc.15890
 
Pubmed Link